The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a large scale, randomized controlled trial to determine whether certain screening tests will reduce the number of deaths from these cancers. PLCO is a multi-institutional clinical trial being conducted at ten sites, geographically and demographically disparate, around the U.S. This controlled trial is a Phase III trial conducting human subjects research. PLCO enrolled 154,942 male and female participants. The PLCO participants are comparable to the general United States population. Life style, dietary and risk factor information was collected from participants. The intervention arm received for lung cancer, posterior-anterior (PA) chest x-ray annually for four screens (except never smokers who received three annual screens), flexible sigmoidoscopy (FSG) at enrollment and again at the fourth or sixth annual screening interval depending on time of enrollment to screen for colorectal cancer. For prostate cancer, men received six annual prostate screens with prostate-specific antigen (PSA) and four digital rectal exams (DRE). Women were screened for ovarian cancer with CA-125 antigen for six annual screens and with transvaginal ultrasound (TVU) for four annual screens. The usual care (control) arm received regular health care from their primary care provider. Whole blood, sequential serum samples and one plasma sample were collected from the intervention arm. Aliquots from these samples are stored in the PLCO Biorepository through collaboration with the Division of Cancer Epidemiology and Genetics (DCEG). The usual care arm provided buccal cell DNA samples which are also stored in the PLCO Biorepository. The PLCO Biorepository currently has over 2.9 million specimens that can be used for etiologic and early marker studies. PLCO is collecting colo-rectal, ovarian, prostate and lung tumor tissue from those participants who have developed cancer. Tissue microarrays are then constructed. STUDY DESIGN: The PLCO is a two-armed, randomized trial in which more than 38,000 men were screened for lung, colorectal, and prostate cancers and approximately 39,000 women were screened for lung, colorectal, and ovarian cancers. Equal numbers of men and women participating as controls continue their usual medical care practices. The eligible age range at entry was 55-74 years. Both screened and control participants are to be followed for at least 13 years from randomization for cancer and death ascertainment to determine if the screening regimen results in reduced disease-specific mortality. Baseline information including demographic characteristics, known risk factors for the cancers under study, and screening history were collected from all participants. In addition, participants completed dietary, food frequency questionnaires and subsequently a risk factor questionnaire that supplements the baseline data provided at the time they enrolled. Blood samples collected at each screening visit were processed into separate components and stored for future molecular analyses. Control participants provided Buccal cell DNA. Participants in both the intervention and control arms completed a dietary questionnaire. All participants also provide annual health status information. Special efforts made to enhance the recruitment of minorities occurred at several screening locations. One site in Detroit, MI focused efforts on increasing the participation of African Americans. A site in Denver, CO hired Spanish speaking staff to enhance the number of Hispanic Americans enrolled in PLCO. BIOREPOSITORY: The PLCO Biorepository contains approximately 2.9 million biologic specimens collected during the six screening years. These samples include serum, plasma and buffy coat and DNA samples. These specimens are an invaluable resource for cancer research. Some of the characteristics that make the PLCO biospecimens uniquely valuable include: [unreadable] Large sample size allows statistical power [unreadable] Specimens are collected prospectively, before cancer diagnosis [unreadable] Serial specimens are collected at each of the 6 annual screenings [unreadable] Detailed background and clinical data are available The PLCO Etiology and Early Marker Studies (EEMS) component is an integral part of the PLCO Trial. The PLCO EEMS has two main focuses: etiologic studies that investigate the environmental, biochemical and genetic risk factors for cancer;and early detection studies that aim to develop reproducible, diagnostics-ready biomarkers of early disease. The PLCO EEMS directly addresses the following strategic priorities of the National Cancer Institute: [unreadable] Understand the causes and mechanisms of cancer [unreadable] Improve early detection and diagnosis